Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE

Stefano Barco, Serena Granziera, Michiel Coppens, Jonathan Douxfils, Mathilde Nijkeuter, Nicoletta Riva, Thomas Vanassche, George Zhang, Min Lin, Pieter W Kamphuisen, Alexander T Cohen, Jan Beyer-Westendorf

Research output: Contribution to journalArticle

Abstract

Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66% vs. ≥66%) resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0%, +1.1%) and +2.2% (0.9%, +3.5%), respectively. Patients with high SAMe-TT2-R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7%). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66%), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0% (-0.6%, +0.7%) for recurrence and +1.3% (-0.1%, +2.7%) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365). Conclusion In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.

Original languageEnglish
Pages (from-to)675-684
Number of pages10
JournalThrombosis and Haemostasis
Volume119
Issue number4
DOIs
Publication statusPublished - 1 Jan 2019

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Venous Thromboembolism
Warfarin
Quality Control
Vitamin K
Hemorrhage
Therapeutics
Random Allocation
Atrial Fibrillation
Confidence Intervals
Safety
Recurrence

Keywords

  • quality of treatment
  • risk assessment model
  • venous thromboembolism
  • vitamin K antagonist
  • warfarin

Cite this

Barco, Stefano ; Granziera, Serena ; Coppens, Michiel ; Douxfils, Jonathan ; Nijkeuter, Mathilde ; Riva, Nicoletta ; Vanassche, Thomas ; Zhang, George ; Lin, Min ; Kamphuisen, Pieter W ; Cohen, Alexander T ; Beyer-Westendorf, Jan. / Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score : An Analysis of Hokusai-VTE. In: Thrombosis and Haemostasis. 2019 ; Vol. 119, No. 4. pp. 675-684.
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abstract = "Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66{\%} vs. ≥66{\%}) resulting in an absolute risk difference (ARD) of +0.5{\%} (95{\%} confidence interval: 0{\%}, +1.1{\%}) and +2.2{\%} (0.9{\%}, +3.5{\%}), respectively. Patients with high SAMe-TT2-R2 score were 76{\%} of total and had lower median TTR (64.7{\%} vs. 70.7{\%}). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66{\%}), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0{\%} (-0.6{\%}, +0.7{\%}) for recurrence and +1.3{\%} (-0.1{\%}, +2.7{\%}) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365). Conclusion In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.",
keywords = "quality of treatment, risk assessment model, venous thromboembolism, vitamin K antagonist, warfarin",
author = "Stefano Barco and Serena Granziera and Michiel Coppens and Jonathan Douxfils and Mathilde Nijkeuter and Nicoletta Riva and Thomas Vanassche and George Zhang and Min Lin and Kamphuisen, {Pieter W} and Cohen, {Alexander T} and Jan Beyer-Westendorf",
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Barco, S, Granziera, S, Coppens, M, Douxfils, J, Nijkeuter, M, Riva, N, Vanassche, T, Zhang, G, Lin, M, Kamphuisen, PW, Cohen, AT & Beyer-Westendorf, J 2019, 'Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE', Thrombosis and Haemostasis, vol. 119, no. 4, pp. 675-684. https://doi.org/10.1055/s-0039-1678546

Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score : An Analysis of Hokusai-VTE. / Barco, Stefano; Granziera, Serena; Coppens, Michiel; Douxfils, Jonathan; Nijkeuter, Mathilde; Riva, Nicoletta; Vanassche, Thomas; Zhang, George; Lin, Min; Kamphuisen, Pieter W; Cohen, Alexander T; Beyer-Westendorf, Jan.

In: Thrombosis and Haemostasis, Vol. 119, No. 4, 01.01.2019, p. 675-684.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score

T2 - An Analysis of Hokusai-VTE

AU - Barco, Stefano

AU - Granziera, Serena

AU - Coppens, Michiel

AU - Douxfils, Jonathan

AU - Nijkeuter, Mathilde

AU - Riva, Nicoletta

AU - Vanassche, Thomas

AU - Zhang, George

AU - Lin, Min

AU - Kamphuisen, Pieter W

AU - Cohen, Alexander T

AU - Beyer-Westendorf, Jan

N1 - Georg Thieme Verlag KG Stuttgart · New York.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66% vs. ≥66%) resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0%, +1.1%) and +2.2% (0.9%, +3.5%), respectively. Patients with high SAMe-TT2-R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7%). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66%), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0% (-0.6%, +0.7%) for recurrence and +1.3% (-0.1%, +2.7%) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365). Conclusion In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.

AB - Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66% vs. ≥66%) resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0%, +1.1%) and +2.2% (0.9%, +3.5%), respectively. Patients with high SAMe-TT2-R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7%). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66%), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0% (-0.6%, +0.7%) for recurrence and +1.3% (-0.1%, +2.7%) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365). Conclusion In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.

KW - quality of treatment

KW - risk assessment model

KW - venous thromboembolism

KW - vitamin K antagonist

KW - warfarin

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U2 - 10.1055/s-0039-1678546

DO - 10.1055/s-0039-1678546

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